We propose to continue our research in the area of acyclic diastereoselective synthesis, with emphasis on the development of novel allylmetal reagents for application to the total synthesis of stereochemically complex natural products. Specific goals for the next grant period are: (1) Development of New Synthetic Methodology Utilizing 3-BoryI-Substituted Allylboranes. The scope of double allylboration reactions for the highly stereocontrolled synthesis of 1,5-diol systems will be expanded by the synthesis of the (Z)-bisboryl reagent 80. Extensions of this methodology to the stereocontrolled synthesis of methyl branched 1,5-diol systems will be accomplished by cross metathesis reactions of allylboronates 84 and 98. (2) Total Synthesis of Reidispongiolide A. Reidispongiolide A is a structurally novel natural product of marine origin with significant cytotoxicity against various human cancer cell lines. A total synthesis of reidispongiolide A will be developed by a route featuring highly stereoselective double allylboration reactions of 1,3-bisboryl reagents 37 and 100 for fragment assembly. (3) Total Synthesis of Tetrafibricin. Tetrafibricin is a structurally interesting fibrinogen receptor antagonist. A very simple and highly stereocontrolled synthesis of this molecule will be developed using 1,3- bisboryl reagents 37, 80, and 100 for fragment assembly. (4) Completion of a Total Synthesis of Amphidinol 3. A total synthesis of amphidinol 3, an antifungal agent of marine origin, will be completed in the coming grant period. The multiple 1,5-diol units in amphidinol provided the stimulus for development of the highly stereoselective 1,5-diol synthesis in the preceding grant period. This technology will also play an important role in the synthesis of the two tetrahydropyran units in the natural product. (5) Total Synthesis of Apoptolidin and Apoptolidin Analogs. Apoptolidin is of considerable interest owing to its ability to induce apoptosis in transformed cell lines. A total synthesis of apoptolidin will be completed. An improved second-generation synthesis of the C(12)-C(28)fragment will be developed by a route featuring our 1,3-bisboryl reagents for fragment assembly. A series of apoptolidin analogs also will be prepared for biological evaluation.